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@ARTICLE{Ichwan:157719,
      author       = {Ichwan, Muhammad and Walker, Tara L and Nicola, Zeina and
                      Ludwig-Müller, Jutta and Böttcher, Christoph and Overall,
                      Rupert W and Adusumilli, Vijay S and Bulut, Merve and Sykes,
                      Alex M and Hübner, Norbert and Ramirez-Rodriguez, Gerardo
                      and Ortiz-López, Leonardo and Lugo-Hernández, Enrique A
                      and Kempermann, Gerd},
      title        = {{A}pple {P}eel and {F}lesh {C}ontain {P}ro-neurogenic
                      {C}ompounds.},
      journal      = {Stem cell reports},
      volume       = {16},
      number       = {3},
      issn         = {2213-6711},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2021-01176},
      pages        = {548 - 565},
      year         = {2021},
      abstract     = {As mammals evolved with exposure to particular diets,
                      naturally abundant compounds may have become part of the set
                      of environmental co-determinants that shaped brain structure
                      and function. Here we investigated whether bioactive factors
                      found in apples directly affect hippocampal neurogenesis in
                      the adult mouse. We found that quercetin, the most abundant
                      flavanol in apple peel, was anti-proliferative at high
                      concentrations but pro-neurogenic at low concentrations.
                      This was confirmed in vivo, with intraperitoneally
                      delivered quercetin promoting survival and neuronal
                      differentiation, without affecting proliferation. Using a
                      bioassay-guided fractionation approach we also identified
                      additional pro-neurogenic compounds in apple flesh that were
                      not related to flavonoids. We found that
                      3,5-dihydroxybenzoic acid significantly increased neural
                      precursor cell proliferation and neurogenesis. This work
                      shows that both flavonoids and 3,5-dihydroxybenzoic acid are
                      pro-neurogenic, not only by activating precursor cell
                      proliferation but also by promoting cell-cycle exit,
                      cellular survival, and neuronal differentiation.},
      keywords     = {Animals / Antioxidants: pharmacology / Cell Cycle: drug
                      effects / Cell Differentiation: drug effects / Cell
                      Proliferation: drug effects / Cell Survival: drug effects /
                      Female / Flavonoids: pharmacology / Fruit: chemistry /
                      Hippocampus: drug effects / Hydroxybenzoates: pharmacology /
                      Male / Malus: chemistry / Mice / Mice, Inbred C57BL /
                      Neurogenesis: drug effects / Proto-Oncogene Proteins c-akt:
                      metabolism / Quercetin: pharmacology / Receptors,
                      G-Protein-Coupled: metabolism / Resorcinols: pharmacology /
                      Signal Transduction / 3,5-dihydroxybenzoic acid (Other) /
                      adult neurogenesis (Other) / dentate gyrus (Other) /
                      hippocampus (Other) / mouse (Other) / neural precursor cells
                      (Other) / quercetin (Other)},
      cin          = {AG Kempermann 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1710001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33577796},
      pmc          = {pmc:PMC7940132},
      doi          = {10.1016/j.stemcr.2021.01.005},
      url          = {https://pub.dzne.de/record/157719},
}